Functional Anatomy of the Basal Ganglia

Our research group studies the neurobiology of Parkinson's disease, with emphasis on the following aspects:

Mapping the brain circuits involved in the pathophysiology of Parkinson's disease: We use animal models that are relevant to the disease to study the changes that take place in the circuits of the basal ganglia as a result dopaminergic degeneration.

Role of G-coupled protein receptors (GPCRs) in Parkinson's disease: The heteromerization of GPCRs constitutes a new molecular entity that is different from that represented by each GPCR separately in terms of affinity for ligands and signaling properties. This project investigates the presence of GPCR heteromers in the nuclei of basal ganglia in control primates and primates with Parkinson's (with and without dyskinesia) in order to determine their use as new therapeutic targets that improve on existing pharmacology. Specifically, we analyze heteromers made up of cannabinoid receptors type CB1, CB2 and GPR55, adenosine A2A receptors, and dopaminergic receptors type D1, D2, D3, and D5.

Cell and Gene Therapy in Parkinson's Disease. The field of gene therapy in the central nervous system has undergone many conceptual changes. Besides the traditional concept of using a viral vector to carry a therapeutic gene, it is possible to design approaches based on the use of viral vectors as carriers of genes to modify cerebral circuits of interest; the manipulation of the cerebral circuits is the source of the potential therapeutic effect. In collaboration with the Gene Therapy Program, we have begun studies and primates focusing on the following: (i) selective reconstruction of the nigrostriatal pathway, (ii) selective permanent or transitory elimination of the specific cerebral circuits, and (iii) direct in situ cell reprogramming. As part of the new ERC project, a cell-therapy approach will be approved that consists of an autologous transplant of directly reprogrammed dopaminergic cells (not having gone through the iPS stage) using adult fibroblasts obtained via skin biopsy. Avoiding the iPS stage provides the added advantage of eliminating the risk of inducing tumors in the host.